Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Identification of several small main-effect QTLs and a large number of epistatic QTLs for drought tolerance related traits in groundnut (Arachishypogaea L.)

Cultivated groundnut or peanut (Arachis hypogaea L.), an allotetraploid (2n = 4x = 40), is a self pollinated and widely grown crop in the semi-arid regions of the world. Improvement of drought tolerance is an important area of research for groundnut breeding programmes. Therefore, for the identification of candidate QTLs for drought tolerance, a comprehensive and refined genetic map containing 191 SSR loci based on a single mapping population (TAG 24 × ICGV 86031), segregating for drought and surrogate traits was developed. Genotyping data and phenotyping data collected for more than ten drought related traits in 2–3 seasons were analyzed in detail for identification of main effect QTLs (M-QTLs) and epistatic QTLs (E-QTLs) using QTL Cartographer, QTLNetwork and Genotype Matrix Mapping (GMM) programmes. A total of 105 M-QTLs with 3.48–33.36% phenotypic variation explained (PVE) were identified using QTL Cartographer, while only 65 M-QTLs with 1.3–15.01% PVE were identified using QTLNetwork. A total of 53 M-QTLs were such which were identified using both programmes. On the other hand, GMM identified 186 (8.54–44.72% PVE) and 63 (7.11–21.13% PVE), three and two loci interactions, whereas only 8 E-QTL interactions with 1.7–8.34% PVE were identified through QTLNetwork. Interestingly a number of co-localized QTLs controlling 2–9 traits were also identified. The identification of few major, many minor M-QTLs and QTL × QTL interactions during the present study confirmed the complex and quantitative nature of drought tolerance in groundnut. This study suggests deployment of modern approaches like marker-assisted recurrent selection or genomic selection instead of marker-assisted backcrossing approach for breeding for drought tolerance in groundnut

Metabolic Profiles and cDNA-AFLP Analysis of Salvia miltiorrhiza and Salvia castanea Diel f. tomentosa Stib

Plants of the genus Salvia produce various types of phenolic compounds and tanshinones which are effective for treatment of coronary heart disease. Salvia miltiorrhiza and S. castanea Diels f. tomentosa Stib are two important members of the genus. In this study, metabolic profiles and cDNA-AFLP analysis of four samples were employed to identify novel genes potentially involved in phenolic compounds and tanshinones biosynthesis, including the red roots from the two species and two tanshinone-free roots from S. miltiorrhiza. The results showed that the red roots of S. castanea Diels f. tomentosa Stib produced high contents of rosmarinic acid (21.77 mg/g) and tanshinone IIA (12.60 mg/g), but low content of salvianolic acid B (1.45 mg/g). The red roots of S. miltiorrhiza produced high content of salvianolic acid B (18.69 mg/g), while tanshinones accumulation in this sample was much less than that in S. castanea Diels f. tomentosa Stib. Tanshinones were not detected in the two tanshinone-free samples, which produced high contents of phenolic compounds. A cDNA-AFLP analysis with 128 primer pairs revealed that 2300 transcript derived fragments (TDFs) were differentially expressed among the four samples. About 323 TDFs were sequenced, of which 78 TDFs were annotated with known functions through BLASTX searching the Genbank database and 14 annotated TDFs were assigned into secondary metabolic pathways through searching the KEGGPATHWAY database. The quantitative real-time PCR analysis indicated that the expression of 9 TDFs was positively correlated with accumulation of phenolic compounds and tanshinones. These TDFs additionally showed coordinated transcriptional response with 6 previously-identified genes involved in biosynthesis of tanshinones and phenolic compounds in S. miltiorrhiza hairy roots treated with yeast extract. The sequence data in the present work not only provided us candidate genes involved in phenolic compounds and tanshinones biosynthesis but also gave us further insight into secondary metabolism in Salvia

Lestaurtinib Inhibits Histone Phosphorylation and Androgen-Dependent Gene Expression in Prostate Cancer Cells

Background: Epigenetics is defined as heritable changes in gene expression that are not based on changes in the DNA sequence. Posttranslational modification of histone proteins is a major mechanism of epigenetic regulation. The kinase PRK1 (protein kinase C related kinase 1, also known as PKN1) phosphorylates histone H3 at threonine 11 and is involved in the regulation of androgen receptor signalling. Thus, it has been identified as a novel drug target but little is known about PRK1 inhibitors and consequences of its inhibition. Methodology/Principal Finding: Using a focused library screening approach, we identified the clinical candidate lestaurtinib (also known as CEP-701) as a new inhibitor of PRK1. Based on a generated 3D model of the PRK1 kinase using the homolog PKC-theta (protein kinase c theta) protein as a template, the key interaction of lestaurtinib with PRK1 was analyzed by means of molecular docking studies. Furthermore, the effects on histone H3 threonine phosphorylation and androgen-dependent gene expression was evaluated in prostate cancer cells. Conclusions/Significance: Lestaurtinib inhibits PRK1 very potently in vitro and in vivo. Applied to cell culture it inhibits histone H3 threonine phosphorylation and androgen-dependent gene expression, a feature that has not been known yet. Thus our findings have implication both for understanding of the clinical activity of lestaurtinib as well as for future PRK

dOCRL maintains immune cell quiescence in Drosophila by regulating endosomal traffic

Lowe Syndrome is a developmental disorder characterized by eye, kidney, and neurological pathologies, and is caused by mutations in the phosphatidylinositol-5-phosphatase OCRL. OCRL plays diverse roles in endocytic and endolysosomal trafficking, cytokinesis, and ciliogenesis, but it is unclear which of these cellular functions underlie specific patient symptoms. Here, we show that mutation of Drosophila OCRL causes cell-autonomous activation of hemocytes, which are macrophage-like cells of the innate immune system. Among many cell biological defects that we identified in docrl mutant hemocytes, we pinpointed the cause of innate immune cell activation to reduced Rab11-dependent recycling traffic and concomitantly increased Rab7-dependent late endosome traffic. Loss of docrl amplifies multiple immune-relevant signals, including Toll, Jun kinase, and STAT, and leads to Rab11-sensitive mis-sorting and excessive secretion of the Toll ligand Spåtzle. Thus, docrl regulation of endosomal traffic maintains hemocytes in a poised, but quiescent state, suggesting mechanisms by which endosomal misregulation of signaling may contribute to symptoms of Lowe syndrome

Activin signaling as an emerging target for therapeutic interventions

After the initial discovery of activins as important regulators of reproduction, novel and diverse roles have been unraveled for them. Activins are expressed in various tissues and have a broad range of activities including the regulation of gonadal function, hormonal homeostasis, growth and differentiation of musculoskeletal tissues, regulation of growth and metastasis of cancer cells, proliferation and differentiation of embryonic stem cells, and even higher brain functions. Activins signal through a combination of type I and II transmembrane serine/threonine kinase receptors. Activin receptors are shared by multiple transforming growth factor-β (TGF-β) ligands such as myostatin, growth and differentiation factor-11 and nodal. Thus, although the activity of each ligand is distinct, they are also redundant, both physiologically and pathologically in vivo. Activin receptors activated by ligands phosphorylate the receptor-regulated Smads for TGF-β, Smad2 and 3. The Smad proteins then undergo multimerization with the co-mediator Smad4, and translocate into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. Signaling through receptors and Smads is controlled by multiple mechanisms including phosphorylation and other posttranslational modifications such as sumoylation, which affect potein localization, stability and transcriptional activity. Non-Smad signaling also plays an important role in activin signaling. Extracellularly, follistatin and related proteins bind to activins and related TGF-β ligands, and control the signaling and availability of ligands

An Antimicrobial Peptide Regulates Tumor-Associated Macrophage Trafficking via the Chemokine Receptor CCR2, a Model for Tumorigenesis

Tumor-associated macrophages (TAMs) constitute a significant part of infiltrating inflammatory cells that are frequently correlated with progression and poor prognosis of a variety of cancers. Tumor cell-produced human β-defensin-3 (hBD-3) has been associated with TAM trafficking in oral cancer; however, its involvement in tumor-related inflammatory processes remains largely unknown., applying a cross-desensitization strategy of CCR2 and its pharmacological inhibitor (RS102895), respectively, was also carried out. outcome and demonstrates the importance of the innate immune system in the development of tumors